Yamaguchi and Yamaguchi 1986). Its deficiency causes a decrease in bone density.

It helps in normal bone growth due to its involvement in numerous metabolic

mechanisms (Prasad 1995; Yamaguchi 1998). Its substitution in HA impedes crystal

growth and thermal stability (Bigi et al. 1997; Kanzaki et al. 2000). Magnesium

(Mg) is involved in bone growth and skeletal metabolism by avoiding osteopenia

and increasing osteoblast cell activity and reducing bone fragility and thus plays a

critical role in bone remodeling (Cox et al. 2014). Mg ion has an obvious prohibiting

influence on the growth and nucleation of HA (Kumta et al. 2005; Wang and

Nancollas 2008). Its substitution in HA exhibits enhanced solubility in comparison

to stoichiometric HA (Landi et al. 2008). Strontium (Sr) is known to modify bone

turnover in favor of bone formation by promoting osteoblast activity and prolifera-

tion (Rapuntean et al. 2018; Reginster et al. 2009) as well as by lowering bone

resorption (Hurtel-Lemaire et al. 2009). At low concentrations of Sr, there occurs a

decrease in coherent length of the crystal, whereas at high concentrations, its

crystallite size and crystallinity increase (Bigi et al. 2007). Europium (Eu³⁺) is a

suitable ion with fluorescent property that can be easily substituted into HA lattice as

a result of its similar ionic radius. It can be used as a biological fluorescent probe due

to its excellent luminescent properties. It exhibits favorable optical properties for use

in laser hosts. It is used as luminescent probe in the study of the crystallographic

structure of activator centers. It is also used as a tool to analyze the local occupancy

and symmetry of the cationic locations in the apatite structure (Ciobanu et al. 2014).

The most important anionic substitutions in HA involve CO3

2
and SiO4

4
for

PO4

3
or F
for OH
groups (LeGeros 1965). Biomimetic HA contains a significant

amount of carbonate (CO3

2
) ions. The carbonate content in the individuals differs

according to age. B-type carbonate-apatite (carbonate replaces phosphate) is ample

in young individuals, whereas old individuals have more A-type carbonate-apatite

(carbonate replaces hydroxyl) (Rey et al. 1991). B-type substitution improves the

solubility of apatite at bodily pH without altering surface polar property, which helps

in the affinity of osteoblastic cells. Carbonate substitution in HA generally results in

a poorly crystalline structure with improved solubility (Wang and Nancollas 2008;

Featherstone et al. 1983; Murugan and Ramakrishna 2006). Silicon (Si) is a vital

trace element present in bones, which increases the rate of bone regeneration and

biomineralization by stimulating the extracellular matrix secretion of chondrocytes.

The presence of Si in HA impedes grain growth, thus promoting solubility and

bioactivity of HA (Porter et al. 2003). Si is also substituted in HA to promote early

bone healing. Fluorine is an indispensable trace element in bone tissue which can

enhance the crystallization of calcium phosphate and further hasten the mineraliza-

tion during the progression of bone formation (Shah et al. 2014; Kleerekoper 1996).

It is present in teeth and bones of humans as a vital element against dissolution. The

bond between implant and the bone is improved by its substitution (Sundfeldt et al.

2002a, b; Qu and Wei 2006). It also strengthens the bone structure (Bhadang et al.

2010) and boosts the thermal stability of HA (Barinov et al. 2003). Therefore,

hydroxyapatite substituted with fluoride ions (FHA) is a good substitute material

for bone repair (LeGeros et al. 1988).

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Unleashing Potential of Bone Mimicking Nanodimensional Hydroxyapatites and. . .

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